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Last updated on April 23, 2014 at 21:24 EDT

Cleveland Clinic Researcher Reports That Evacetrapib Can Increase HDL (Good) Cholesterol 128 Percent

November 15, 2011

Researchers at Cleveland Clinic reported today that administration of a new drug— evacetrapib — can dramatically increase HDL (good) cholesterol, while significantly lowering LDL (bad) cholesterol). At the highest tested dosage, the levels of HDL more than doubled.

The study was presented today by lead investigator Stephen Nicholls MD PhD, Cardiovascular Director of the Cleveland Clinic Coordinating Center for Clinical Research (C5), at the American Heart Association’s Scientific Sessions in Orlando, Fla. The results of this Phase II clinical trial were simultaneously published in the Journal of the American Medical Association.

There were initially 1154 patients screened at 70 site locations, with 398 patients randomized for the trial. Evacetrapib (500 mg) produced an HDL increase that ranged from 53.6 percent to 128.8 percent, while decreasing LDL by 13.6 percent to 35.9 percent. When combined with statin therapy, evacetrapib (100mg) increased HDL by 79.9 percent to 94 percent and further decreased LDL.

“In this study, evacetrapib was able to show striking increases in HDL while significantly lowering LDL,” said Dr. Nicholls. “The next step will be a large cardiovascular outcome trial to determine if this drug can reduce cardiovascular morbidity and mortality.”

Evacetrapib belongs to a new class of drugs under development known as cholesteryl ester transfer protein (CETP) inhibitors. The first drug in the class, torcetrapib, failed due to unexpected toxicity, but many researchers believe that newer compounds such as evacetrapib may avoid this toxicity. In the current trial, evacetrapib showed none of the adverse effects noted with torcetrapib. Specifically, evacetrapib resulted in no increase in blood pressure or adrenal synthesis of aldosterone or cortisol.

Despite the benefits of statins, cardiovascular disease remains the No. 1 cause of death in both men and women in developed countries. Accordingly, considerable efforts have focused on development of new therapeutic agents designed to address residual cardiovascular risk.

Dr.Nicholls served as Principal Investigator for the trial and Steven Nissen, M.D. served as Study Chairman. Both Cleveland Clinic physicians.

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